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Hyperpolarized Carbon-13 MRI: Comparison
Please note this is a comparison between Version 2 by Conner Chen and Version 1 by Michael Vaeggemose.

MR spectroscopy (MRS) and spectroscopic imaging (MRSI) obtain metabolic information noninvasively from nuclei spins. For in vivo applications, common MR-active nuclei are protons (1H), phosphorus (31P), carbon (13C), sodium (23Na), and xenon (129Xe). The most common are protons due to their high gyromagnetic ratio and natural abundance in the human body. Since most metabolic processes involve carbon, 13C spectroscopy is a valuable method to measure in vivo metabolism noninvasively [1,2,3]. 13C spectra are characterized by a large spectral range (162–185 ppm), narrow line widths, and low sensitivity due to the low gyromagnetic ratio (a quarter as compared to protons) and natural abundance of 1.1% in vivo. However, the sensitivity can be increased with the use of 13C-enriched agents and by hyperpolarization.

Hyperpolarized (HP) 13C MRI is a method that magnetizes 13C probes to dramatically increase signal as compared to conventional MRI [3]. Metabolic and functional HP 13C MRI is a promising diagnostic tool for detecting disorders linked to altered metabolism such as cancer, diabetes, and heart diseases [4], increasing sensitivity sufficiently to map metabolic pathways in vivo without the use of ionizing radiation, as in positron emission tomography (PET) imaging. Metabolic imaging using HP 13C compounds has been translated successfully into single-organ examinations in healthy controls and various patient populations [5,6,7,8,9,10].

  • hyperpolarized carbon-13 MRI
  • review
  • clinical application
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References

  1. Ardenkjaer-Larsen, J.H. On the present and future of dissolution-DNP. J. Magn. Reson. 2016, 264, 3–12.
  2. Lee, C.Y.; Soliman, H.; Geraghty, B.J.; Chen, A.P.; Connelly, K.A.; Endre, R.; Perks, W.J.; Heyn, C.; Black, S.E.; Cunningham, C.H. Lactate topography of the human brain using hyperpolarized 13C-MRI. NeuroImage 2020, 78, 3755–3760.
  3. Wang, Z.J.; Ohliger, M.A.; Larson, P.E.Z.; Gordon, J.W.; Bok, R.A.; Slater, J.; Villanueva-Meyer, J.E.; Hess, C.P.; Kurhanewicz, J.; Vigneron, D.B. Hyperpolarized 13C MRI: State of the Art and Future Directions. Radiology 2019, 291, 273–284.
  4. Grist, J.T.; McLean, M.A.; Riemer, F.; Schulte, R.F.; Deen, S.S.; Zaccagna, F.; Woitek, R.; Daniels, C.J.; Kaggie, J.D.; Matys, T.; et al. Quantifying normal human brain metabolism using hyperpolarized [1–13C]pyruvate and magnetic resonance imaging. NeuroImage 2019, 189, 171–179.
  5. Keshari, K.R.; Wilson, D.M. Chemistry and biochemistry of 13C hyperpolarized magnetic resonance using dynamic nuclear polarization. Chem. Soc. Rev. 2014, 43, 1627–1659.
  6. Grist, J.T.; Miller, J.J.; Zaccagna, F.; McLean, M.A.; Riemer, F.; Matys, T.; Tyler, D.J.; Laustsen, C.; Coles, A.J.; Gallagher, F.A. Hyperpolarized 13C MRI: A novel approach for probing cerebral metabolism in health and neurological disease. Br. J. Pharmacol. 2020, 40, 1137–1147.
  7. Warburg, O. On the Origin of Cancer Cells. Science 1956, 123, 309–314.
  8. Zaccagna, F.; Grist, J.T.; Deen, S.S.; Woitek, R.; Lechermann, L.M.; McLean, M.A.; Basu, B.; Gallagher, F.A. Hyperpolarized carbon-13 magnetic resonance spectroscopic imaging: A clinical tool for studying tumour metabolism. Br. J. Radiol. 2018, 91, 20170688.
  9. Heiden, M.G.V.; Cantley, L.C.; Thompson, C.B. Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science 2009, 324, 1029–1033.
  10. Golman, K.; Lerche, M.; Pehrson, R.; Ardenkjaer-Larsen, J.H. Metabolic Imaging by Hyperpolarized 13C Magnetic Resonance Imaging for In vivo Tumor Diagnosis. Cancer Res. 2006, 66, 10855–10860.
  11. Nelson, S.J.; Kurhanewicz, J.; Vigneron, D.B.; Larson, P.E.Z.; Harzstark, A.L.; Ferrone, M.; Van Criekinge, M.; Chang, J.W.; Bok, R.; Park, I.; et al. Metabolic Imaging of Patients with Prostate Cancer Using Hyperpolarized [1-13C]Pyruvate. Sci. Transl. Med. 2013, 5, 198ra108.
  12. Gordon, J.W.; Chen, H.-Y.; Autry, A.; Park, I.; Van Criekinge, M.; Mammoli, D.; Milshteyn, E.; Bok, R.; Xu, D.; Li, Y.; et al. Translation of Carbon-13 EPI for hyperpolarized MR molecular imaging of prostate and brain cancer patients. Magn. Reson. Med. 2019, 81, 2702–2709.
  13. Kurhanewicz, J.; Bok, R.; Nelson, S.J.; Vigneron, D.B. Current and Potential Applications of Clinical 13C MR Spectroscopy. J. Nucl. Med. 2008, 49, 341–344.
  14. Chen, H.-Y.; Aggarwal, R.; Bok, R.A.; Ohliger, M.A.; Zhu, Z.; Lee, P.; Gordon, J.W.; Van Criekinge, M.; Carvajal, L.; Slater, J.B.; et al. Hyperpolarized 13C-pyruvate MRI detects real-time metabolic flux in prostate cancer metastases to bone and liver: A clinical feasibility study. Prostate Cancer Prostatic Dis. 2020, 23, 269–276.
  15. Aggarwal, R.; Vigneron, D.B.; Kurhanewicz, J. Hyperpolarized 1-[13C]-Pyruvate Magnetic Resonance Imaging Detects an Early Metabolic Response to Androgen Ablation Therapy in Prostate Cancer. Eur. Urol. 2017, 72, 1028–1029.
  16. Barrett, T.; Riemer, F.; McLean, M.A.; Kaggie, J.D.; Robb, F.; Warren, A.Y.; Graves, M.J.; Gallagher, F.A. Molecular imaging of the prostate: Comparing total sodium concentration quantification in prostate cancer and normal tissue using dedicated 13C and 23Na endorectal coils. J. Magn. Reson. Imaging 2020, 51, 90–97.
  17. Kurhanewicz, J.; Vigneron, D.B. Advances in MR Spectroscopy of the Prostate. Magn. Reson. Imaging Clin. North Am. 2008, 16, 697–710.
  18. Wilson, D.M.; Kurhanewicz, J. Hyperpolarized 13C MR for Molecular Imaging of Prostate Cancer. J. Nucl. Med. 2014, 55, 1567–1572.
  19. Stødkilde-Jørgensen, H.; Laustsen, C.; Hansen, E.S.S.; Schulte, R.; Ardenkjaer-Larsen, J.H.; Comment, A.; Frøkiær, J.; Ringgaard, S.; Bertelsen, L.B.; Ladekarl, M.; et al. Pilot Study Experiences With Hyperpolarized [1-13C]pyruvate MRI in Pancreatic Cancer Patients. J. Magn. Reson. Imaging 2020, 51, 961–963.
  20. Gallagher, F.A.; Woitek, R.; McLean, M.A.; Gill, A.B.; Garcia, R.M.; Provenzano, E.; Riemer, F.; Kaggie, J.; Chhabra, A.; Ursprung, S.; et al. Imaging breast cancer using hyperpolarized carbon-13 MRI. Proc. Natl. Acad. Sci. USA 2020, 117, 2092–2098.
  21. Woitek, R.; McLean, M.A.; Gill, A.B.; Grist, J.T.; Provenzano, E.; Patterson, A.J.; Ursprung, S.; Torheim, T.; Zaccagna, F.; Locke, M.; et al. Hyperpolarized 13C MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer. Radiol. Imaging Cancer 2020, 2, e200017.
  22. Jagannathan, N.R. Application of in vivo MR methods in the study of breast cancer metabolism. NMR Biomed. 2019, 32, e4032.
  23. Miloushev, V.Z.; Granlund, K.L.; Boltyanskiy, R.; Lyashchenko, S.K.; DeAngelis, L.M.; Mellinghoff, I.K.; Brennan, C.W.; Tabar, V.; Yang, T.J.; Holodny, A.I.; et al. Metabolic Imaging of the Human Brain with Hyperpolarized 13C Pyruvate Demonstrates 13C Lactate Production in Brain Tumor Patients. Cancer Res. 2018, 256, 36–42.
  24. Zhu, X.; Gordon, J.W.; Bok, R.A.; Kurhanewicz, J.; Larson, P.E. Dynamic diffusion-weighted hyperpolarized 13C imaging based on a slice-selective double spin echo sequence for measurements of cellular transport. Magn. Reson. Med. 2019, 81, 2001–2010.
  25. Autry, A.W.; Gordon, J.W.; Chen, H.-Y.; Lafontaine, M.; Bok, R.; Van Criekinge, M.; Slater, J.B.; Carvajal, L.; Villanueva-Meyer, J.E.; Chang, S.M.; et al. Characterization of serial hyperpolarized 13C metabolic imaging in patients with glioma. NeuroImage Clin. 2020, 27, 102323.
  26. Tran, M.; Latifoltojar, A.; Neves, J.B.; Papoutsaki, M.-V.; Gong, F.; Comment, A.; Costa, A.S.H.; Glaser, M.; Tran-Dang, M.-A.; El Sheikh, S.; et al. First-in-human in vivo non-invasive assessment of intra-tumoral metabolic heterogeneity in renal cell carcinoma. BJR Case Rep. 2019, 5, 20190003.
  27. Kurhanewicz, J.; Vigneron, D.B.; Ardenkjaer-Larsen, J.H.; Bankson, J.A.; Brindle, K.; Cunningham, C.H.; Gallagher, F.A.; Keshari, K.R.; Kjaer, A.; Laustsen, C.; et al. Hyperpolarized 13C MRI: Path to Clinical Translation in Oncology. Neoplasia 2019, 21, 1–16.
  28. Guglielmetti, C.; Najac, C.; Didonna, A.; Van Der Linden, A.; Ronen, S.M.; Chaumeil, M.M. Hyperpolarized 13C MR metabolic imaging can detect neuroinflammation in vivo in a multiple sclerosis murine model. Proc. Natl. Acad. Sci. USA 2017, 114, E6982–E6991.
  29. Xu, Y.; Ringgaard, S.; Mariager, C.Ø.; Bertelsen, L.B.; Schroeder, M.; Qi, H.; Laustsen, C.; Stødkilde-Jørgensen, H. Hyperpolarized 13C Magnetic Resonance Imaging Can Detect Metabolic Changes Characteristic of Penumbra in Ischemic Stroke. Tomography 2017, 3, 67–73.
  30. Stovell, M.G.; Yan, J.-L.; Sleigh, A.; Mada, M.O.; Carpenter, T.A.; Hutchinson, P.J.A.; Carpenter, K.L.H. Assessing Metabolism and Injury in Acute Human Traumatic Brain Injury with Magnetic Resonance Spectroscopy: Current and Future Applications. Front. Neurol. 2017, 8.
  31. DeVience, S.J.; Lu, X.; Proctor, J.; Rangghran, P.; Melhem, E.R.; Gullapalli, R.; Fiskum, G.M.; Mayer, D. Metabolic imaging of energy metabolism in traumatic brain injury using hyperpolarized [1-13C]pyruvate. Sci. Rep. 2017, 7, 1–7.
  32. Guglielmetti, C.; Chou, A.; Krukowski, K.; Najac, C.; Feng, X.; Riparip, L.-K.; Rosi, S.; Chaumeil, M.M. In vivo metabolic imaging of Traumatic Brain Injury. Sci. Rep. 2017, 7, 17525.
  33. Takado, Y.; Cheng, T.; Bastiaansen, J.A.M.; Yoshihara, H.A.I.; Lanz, B.; Mishkovsky, M.; Lengacher, S.; Comment, A. Hyperpolarized 13C Magnetic Resonance Spectroscopy Reveals the Rate-Limiting Role of the Blood–Brain Barrier in the Cerebral Uptake and Metabolism of l-Lactate in Vivo. ACS Chem. Neurosci. 2018, 9, 2554–2562.
  34. Miller, J.J.; Grist, J.T.; Serres, S.; Larkin, J.R.; Lau, A.Z.; Ray, K.; Fisher, K.R.; Hansen, E.; Tougaard, R.S.; Nielsen, P.M.; et al. 13C Pyruvate Transport Across the Blood-Brain Barrier in Preclinical Hyperpolarised MRI. Sci. Rep. 2018, 8, 1–15.
  35. Josan, S.; Hurd, R.E.; Billingsley, K.L.; Senadheera, L.; Park, J.M.; Yen, Y.-F.; Pfefferbaum, A.; Spielman, D.M.; Mayer, D. Effects of isoflurane anesthesia on hyperpolarized 13C metabolic measurements in rat brain. Magn. Reson. Med. 2013, 70, 1117–1124.
  36. Lee, J.; Ramirez, M.S.; Walker, C.M.; Chen, Y.; Yi, S.; Sandulache, V.C.; Lai, S.Y.; Bankson, J.A. High-throughput hyperpolarized 13 C metabolic investigations using a multi-channel acquisition system. J. Magn. Reson. 2015, 260, 20–27.
  37. Chen, H.; Autry, A.W.; Brender, J.R.; Kishimoto, S.; Krishna, M.C.; Vareth, M.; Bok, R.A.; Reed, G.D.; Carvajal, L.; Gordon, J.W.; et al. Tensor image enhancement and optimal multichannel receiver combination analyses for human hyperpolarized 13 C MRSI. Magn. Reson. Med. 2020, 84, 3351–3365.
  38. Gordon, J.W.; Hansen, R.B.; Shin, P.J.; Feng, Y.; Vigneron, D.B.; Larson, P.E. 3D hyperpolarized C-13 EPI with calibrationless parallel imaging. J. Magn. Reson. 2018, 289, 92–99.
  39. Nelson, S.J.; Ozhinsky, E.; Li, Y.; Park, I.W.; Crane, J. Strategies for rapid in vivo 1H and hyperpolarized 13C MR spectroscopic imaging. J. Magn. Reson. 2013, 229, 187–197.
  40. Chung, B.T.; Chen, H.-Y.; Gordon, J.; Mammoli, D.; Sriram, R.; Autry, A.W.; Le Page, L.M.; Chaumeil, M.M.; Shin, P.; Slater, J.; et al. First hyperpolarized [2-13C]pyruvate MR studies of human brain metabolism. J. Magn. Reson. 2019, 309, 106617.
  41. Captur, G.; Manisty, C.; Moon, J.C. Cardiac MRI evaluation of myocardial disease. Heart 2016, 102, 1429–1435.
  42. Neubauer, S. The Failing Heart—An Engine Out of Fuel. N. Engl. J. Med. 2007, 356, 1140–1151.
  43. Schroeder, M.A.; Clarke, K.; Neubauer, S.; Tyler, D.J. Hyperpolarized Magnetic Resonance: A Novel Technique for the In Vivo Assessment of Cardiovascular Disease. Circulation 2011, 124, 1580–1594.
  44. Rider, O.J.; Tyler, D.J. Clinical Implications of Cardiac Hyperpolarized Magnetic Resonance Imaging. J. Cardiovasc. Magn. Reson. 2013, 15, 93.
  45. Lauritzen, M.; Sogaard, L.; Madsen, P.; Ardenkjaer-Larsen, J. Hyperpolarized Metabolic MR in the Study of Cardiac Function and Disease. Curr. Pharm. Des. 2014, 20, 6162–6170.
  46. Lau, A.Z.; Lau, J.Y.C.; Chen, A.P.; Cunningham, C.H. Simultaneous multislice acquisition without trajectory modification for hyperpolarized 13 C experiments. Magn. Reson. Med. 2018, 80, 1588–1594.
  47. Dominguez, W.; Geraghty, B.J.; Lau, J.Y.; Robb, F.J.; Chen, A.P.; Cunningham, C.H. Intensity correction for multichannel hyperpolarized 13 C imaging of the heart. Magn. Reson. Med. 2015, 75, 859–865.
  48. Cunningham, C.H.; Lau, J.Y.; Chen, A.P.; Geraghty, B.J.; Perks, W.J.; Roifman, I.; Wright, G.A.; Connelly, K.A. Hyperpolarized 13C Metabolic MRI of the Human Heart. Circ. Res. 2016, 119, 1177–1182.
  49. Rider, O.J.; Apps, A.; Miller, J.J.; Lau, J.Y.; Lewis, A.J.; Peterzan, M.A.; Dodd, M.S.; Lau, A.Z.; Trumper, C.; Gallagher, F.A.; et al. Noninvasive In Vivo Assessment of Cardiac Metabolism in the Healthy and Diabetic Human Heart Using Hyperpolarized 13 C MRI. Circ. Res. 2020, 126, 725–736.
  50. Lewis, A.J.M.; Tyler, D.J.; Rider, O. Clinical Cardiovascular Applications of Hyperpolarized Magnetic Resonance. Cardiovasc. Drugs Ther. 2020, 34, 231–240.
  51. Dekkers, I.A.; De Boer, A.; Sharma, K.; Cox, E.F.; Lamb, H.J.; Buckley, D.L.; Bane, O.; Morris, D.M.; Prasad, P.V.; Semple, S.I.K.; et al. Consensus-based technical recommendations for clinical translation of renal T1 and T2 mapping MRI. Magma Magn. Reson. Mater. Phys. Biol. Med. 2020, 33, 163–176.
  52. Mendichovszky, I.; Pullens, P.; Dekkers, I.; Nery, F.; Bane, O.; Pohlmann, A.; De Boer, A.; Ljimani, A.; Odudu, A.; Buchanan, C.; et al. Technical recommendations for clinical translation of renal MRI: A consensus project of the Cooperation in Science and Technology Action PARENCHIMA. Magma Magn. Reson. Mater. Phys. Biol. Med. 2020, 33, 131–140.
  53. Laustsen, C. Hyperpolarized Renal Magnetic Resonance Imaging: Potential and Pitfalls. Front. Physiol. 2016, 7, 72.
  54. Johansson, E.; Olsson, L.E.; Månsson, S.; Petersson, J.; Golman, K.; Ståhlberg, F.; Wirestam, R. Perfusion assessment with bolus differentiation: A technique applicable to hyperpolarized tracers. Magn. Reson. Med. 2004, 52, 1043–1051.
  55. Golman, K.; Petersson, J.S. Metabolic Imaging and Other Applications of Hyperpolarized 13C1. Acad. Radiol. 2006, 13, 932–942.
  56. Laustsen, C.; Østergaard, J.A.; Lauritzen, M.H.; Nørregaard, R.; Bowen, S.; Søgaard, L.V.; Flyvbjerg, A.; Pedersen, M.; Ardenkjaer-Larsen, J.H. Assessment of early diabetic renal changes with hyperpolarized [1-13C]pyruvate. Diabetes Metab. Res. Rev. 2013, 29, 125–129.
  57. Grobner, T. Gadolinium—A specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol. Dial. Transplant. 2006, 21, 1104–1108.
  58. Keshari, K.R.; Wilson, D.M.; Sai, V.; Bok, R.; Jen, K.-Y.; Larson, P.; Van Criekinge, M.; Kurhanewicz, J.; Wang, Z.J. Noninvasive In Vivo Imaging of Diabetes-Induced Renal Oxidative Stress and Response to Therapy Using Hyperpolarized 13C Dehydroascorbate Magnetic Resonance. Diabetes 2015, 64, 344–352.
  59. Laustsen, C.; Lycke, S.; Palm, F.; Østergaard, J.A.; Bibby, B.M.; Nørregaard, R.; Flyvbjerg, A.; Pedersen, M.; Ardenkjaer-Larsen, J.H.; Ardenkjær-Larsen, J.H. High altitude may alter oxygen availability and renal metabolism in diabetics as measured by hyperpolarized [1-13C]pyruvate magnetic resonance imaging. Kidney Int. 2014, 86, 67–74.
  60. Baligand, C.; Qin, H.; True-Yasaki, A.; Gordon, J.W.; Von Morze, C.; Santos, J.D.; Wilson, D.M.; Raffai, R.; Cowley, P.M.; Baker, A.J.; et al. Hyperpolarized13C magnetic resonance evaluation of renal ischemia reperfusion injury in a murine model. NMR Biomed. 2017, 30, e3765.
  61. Reed, G.D.; Von Morze, C.; Bok, R.; Koelsch, B.L.; Van Criekinge, M.; Smith, K.J.; Larson, P.E.Z.; Kurhanewicz, J.; Vigneron, D.B.; Shang, H. High resolution (13)C MRI with hyperpolarized urea: In vivo T(2) mapping and (15)N labeling effects. IEEE Trans. Med. Imaging 2013, 33, 362–371.
  62. Pedersen, M.; Ursprung, S.; Jensen, J.D.; Jespersen, B.; Gallagher, F.; Laustsen, C. Hyperpolarised 13C-MRI metabolic and functional imaging: An emerging renal MR diagnostic modality. Magma: Magn. Reson. Mater. Phys. Biol. Med. 2019, 33, 23–32.
  63. Durst, M.; Chiavazza, E.; Haase, A.; Aime, S.; Schwaiger, M.; Schulte, R.F. α-trideuteromethyl[15N]glutamine: A long-lived hyperpolarized perfusion marker. Magn. Reson. Med. 2016, 76, 1900–1904.
  64. Ohliger, M.A.; Von Morze, C.; Marco-Rius, I.; Gordon, J.; Larson, P.E.Z.; Bok, R.; Chen, H.-Y.; Kurhanewicz, J.; Vigneron, D. Combining hyperpolarized 13C MRI with a liver-specific gadolinium contrast agent for selective assessment of hepatocyte metabolism. Magn. Reson. Med. 2017, 77, 2356–2363.
  65. Moreno, K.X.; Satapati, S.; DeBerardinis, R.J.; Burgess, S.C.; Malloy, C.R.; Merritt, M.E. Real-time Detection of Hepatic Gluconeogenic and Glycogenolytic States Using Hyperpolarized [2-13C]Dihydroxyacetone. J. Biol. Chem. 2014, 289, 35859–35867.
  66. Moon, C.-M.; Shin, S.-S.; Lim, N.-Y.; Kim, S.-K.; Kang, Y.-J.; Kim, H.-O.; Lee, S.-J.; Beak, B.-H.; Kim, Y.-H.; Jeong, G.-W. Metabolic alterations in a rat model of hepatic ischaemia reperfusion injury: In vivo hyperpolarized 13 C MRS and metabolic imaging. Liver Int. 2018, 38, 1117–1127.
  67. Moon, C.-M.; Shin, S.-S.; Heo, S.-H.; Lim, H.-S.; Moon, M.-J.; Surendran, S.P.; Kim, G.-E.; Park, I.-W.; Jeong, Y.-Y. Metabolic Changes in Different Stages of Liver Fibrosis: In vivo Hyperpolarized 13C MR Spectroscopy and Metabolic Imaging. Mol. Imaging Biol. 2019, 21, 842–851.
  68. Moon, C.-M.; Oh, C.-H.; Ahn, K.-Y.; Yang, J.-S.; Kim, J.-Y.; Shin, S.-S.; Lim, H.-S.; Heo, S.-H.; Seon, H.-J.; Kim, J.-W.; et al. Metabolic biomarkers for non-alcoholic fatty liver disease induced by high-fat diet: In vivo magnetic resonance spectroscopy of hyperpolarized [1-13C] pyruvate. Biochem. Biophys. Res. Commun. 2017, 482, 112–119.
  69. Josan, S.; Billingsley, K.L.; Orduna, J.; Park, J.M.; Luong, R.; Yu, L.; Hurd, R.E.; Pfefferbaum, A.; Spielman, D.M.; Mayer, D. Assessing inflammatory liver injury in an acute CCl4model using dynamic 3D metabolic imaging of hyperpolarized [1-13C]pyruvate. NMR Biomed. 2015, 28, 1671–1677.
  70. Spielman, D.M.; Mayer, D.; Yen, Y.-F.; Tropp, J.; Hurd, R.E.; Pfefferbaum, A. In vivo measurement of ethanol metabolism in the rat liver using magnetic resonance spectroscopy of hyperpolarized [1-13C]pyruvate. Magn. Reson. Med. 2009, 62, 307–313.
  71. Jin, E.S.; Moreno, K.X.; Wang, J.; Fidelino, L.; Merritt, M.E.; Sherry, A.D.; Malloy, C.R. Metabolism of hyperpolarized [1-13C]pyruvate through alternate pathways in rat liver. NMR Biomed. 2016, 29, 466–474.
  72. Sharma, G.; Wu, C.-Y.; Wynn, R.M.; Gui, W.; Malloy, C.R.; Sherry, A.D.; Chuang, D.T.; Khemtong, C. Real-time hyperpolarized 13C magnetic resonance detects increased pyruvate oxidation in pyruvate dehydrogenase kinase 2/4–double knockout mouse livers. Sci. Rep. 2019, 9, 1–11.
  73. Høyer, K.F.; Laustsen, C.; Ringgaard, S.; Qi, H.; Mariager, C.Ø.; Nielsen, T.S.; Sundekilde, U.K.; Treebak, J.T.; Jessen, N.; Stødkilde-Jørgensen, H. Assessment of mouse liver [1-13C]pyruvate metabolism by dynamic hyperpolarized MRS. J. Endocrinol. 2019, 242, 251–260.
  74. Lee, P.; Leong, W.; Tan, T.; Lim, M.; Han, W.; Radda, G.K. In Vivohyperpolarized carbon-13 magnetic resonance spectroscopy reveals increased pyruvate carboxylase flux in an insulin-resistant mouse model. Hepatology 2013, 57, 515–524.
  75. Marco-Rius, I.; Wright, A.J.; Hu, D.-E.; Savic, D.; Miller, J.J.; Timm, K.N.; Tyler, D.; Brindle, K.M.; Comment, A. Probing hepatic metabolism of [2-13C]dihydroxyacetone in vivo with 1H-decoupled hyperpolarized 13C-MR. Magma Magn. Reson. Mater. Phys. Biol. Med. 2021, 34, 49–56.
  76. Hövener, J.-B.; Chekmenev, E.Y.; Harris, K.C.; Perman, W.H.; Tran, T.T.; Ross, B.D.; Bhattacharya, P. Quality assurance of PASADENA hyperpolarization for 13C biomolecules. Magma Magn. Reson. Mater. Phys. Biol. Med. 2008, 22, 123–134.
  77. Lehmkuhl, S.; Suefke, M.; Kentner, A.; Yen, Y.-F.; Blümich, B.; Rosen, M.S.; Appelt, S.; Theis, T. SABRE polarized low field rare-spin spectroscopy. J. Chem. Phys. 2020, 152, 184202.
  78. Berner, S.; Schmidt, A.B.; Zimmermann, M.; Pravdivtsev, A.N.; Glöggler, S.; Hennig, J.; Von Elverfeldt, D.; Hövener, J. SAMBADENA Hyperpolarization of 13C-Succinate in an MRI: Singlet-Triplet Mixing Causes Polarization Loss. ChemistryOpen 2019, 8, 728–736.
  79. Hirsch, M.L.; Kalechofsky, N.; Belzer, A.; Rosay, M.; Kempf, J.G. Brute-Force Hyperpolarization for NMR and MRI. J. Am. Chem. Soc. 2015, 137, 8428–8434.
  80. Duckett, S.B.; Mewis, R.E. Application of Parahydrogen Induced Polarization Techniques in NMR Spectroscopy and Imaging. Acc. Chem. Res. 2012, 45, 1247–1257.
  81. Reineri, F.; Boi, T.; Aime, S. ParaHydrogen Induced Polarization of 13C carboxylate resonance in acetate and pyruvate. Nat. Commun. 2015, 6, 5858.
  82. Ardenkjaer-Larsen, J.H.; Fridlund, B.; Gram, A.; Hansson, L.; Lerche, M.H.; Servin, R.; Thaning, M.; Golman, K. Increase in signal-to-noise ratio of >10,000 times in liquid-state NMR. Proc. Natl. Acad. Sci. USA 2003, 100, 10158–10163.
  83. Ardenkjaer-Larsen, J.H.; Leach, A.M.; Clarke, N.; Urbahn, J.; Anderson, D.; Skloss, T.W. Dynamic nuclear polarization polarizer for sterile use intent. NMR Biomed. 2011, 24, 927–932.
  84. Ardenkjaer-Larsen, J.H.; Bowen, S.; Petersen, J.R.; Rybalko, O.; Vinding, M.S.; Ullisch, M.; Nielsen, N.C. Cryogen-free dissolution dynamic nuclear polarization polarizer operating at 3.35 T, 6.70 T, and 10.1 T. Magn. Reson. Med. 2019, 81, 2184–2194.
  85. Cheng, T.; Gaunt, A.P.; Marco-Rius, I.; Gehrung, M.; Chen, A.P.; Van Der Klink, J.J.; Comment, A. A multisample 7 T dynamic nuclear polarization polarizer for preclinical hyperpolarized MR. NMR Biomed. 2020, 33, e4264.
  86. Pinon, A.C.; Capozzi, A.; Ardenkjær-Larsen, J.H. Hyperpolarization via dissolution dynamic nuclear polarization: New technological and methodological advances. Magma Magn. Reson. Mater. Phys. Biol. Med. 2021, 34, 5–23.
  87. Hurd, R.E.; Yen, Y.-F.; Chen, A.; Ardenkjaer-Larsen, J.H. Hyperpolarized13C metabolic imaging using dissolution dynamic nuclear polarization. J. Magn. Reson. Imaging 2012, 36, 1314–1328.
  88. Maudsley, A. Sensitivity in fourier imaging. J. Magn. Reson. 1986, 68, 363–366.
  89. Golman, K.; Thaning, M. Real-time metabolic imaging. Proc. Natl. Acad. Sci. USA 2006, 103, 11270–11275.
  90. Yen, Y.-F.; Kohler, S.; Chen, A.; Tropp, J.; Bok, R.; Wolber, J.; Albers, M.; Gram, K.; Zierhut, M.; Park, I.; et al. Imaging considerations for in vivo13C metabolic mapping using hyperpolarized13C-pyruvate. Magn. Reson. Med. 2009, 62, 1–10.
  91. Mayer, D.; Levin, Y.S.; Hurd, R.E.; Glover, G.H.; Spielman, D.M. Fast metabolic imaging of systems with sparse spectra: Application for hyperpolarized13C imaging. Magn. Reson. Med. 2006, 56, 932–937.
  92. Ramirez, M.S.; Lee, J.; Walker, C.M.; Sandulache, V.C.; Hennel, F.; Lai, S.Y.; Bankson, J.A. Radial spectroscopic MRI of hyperpolarized [1-13C] pyruvate at 7 tesla. Magn. Reson. Med. 2014, 72, 986–995.
  93. Jiang, W.; Lustig, M.; Larson, P.E.Z. Concentric rings K-space trajectory for hyperpolarized 13C MR spectroscopic imaging. Magn. Reson. Med. 2016, 75, 19–31.
  94. Gordon, J.W.; Chen, H.; Dwork, N.; Tang, S.; Larson, P.E.Z. Fast Imaging for Hyperpolarized MR Metabolic Imaging. J. Magn. Reson. Imaging 2021, 53, 686–702.
  95. Schulte, R.F.; Sperl, J.I.; Weidl, E.; Menzel, M.I.; Janich, M.A.; Khegai, O.; Durst, M.; Ardenkjaer-Larsen, J.H.; Glaser, S.J.; Haase, A.; et al. Saturation-recovery metabolic-exchange rate imaging with hyperpolarized [1-13C] pyruvate using spectral-spatial excitation. Magn. Reson. Med. 2012, 69, 1209–1216.
  96. Cunningham, C.H.; Chen, A.P.; Lustig, M.; Hargreaves, B.A.; Lupo, J.; Xu, D.; Kurhanewicz, J.; Hurd, R.E.; Pauly, J.M.; Nelson, S.J.; et al. Pulse sequence for dynamic volumetric imaging of hyperpolarized metabolic products. J. Magn. Reson. 2008, 193, 139–146.
  97. Arunachalam, A.; Whitt, D.; Fish, K.; Giaquinto, R.; Piel, J.; Watkins, R.; Hancu, I. Accelerated spectroscopic imaging of hyperpolarized C-13 pyruvate using SENSE parallel imaging. NMR Biomed. 2009, 22, 867–873.
  98. Chen, H.-Y.; Larson, P.E.; Gordon, J.W.; Bok, R.A.; Ferrone, M.; Van Criekinge, M.; Carvajal, L.; Cao, P.; Pauly, J.M.; Kerr, A.B.; et al. Technique development of 3D dynamic CS-EPSI for hyperpolarized 13 C pyruvate MR molecular imaging of human prostate cancer. Magn. Reson. Med. 2018, 80, 2062–2072.
  99. Hu, S.; Lustig, M.; Chen, A.P.; Crane, J.; Kerr, A.; Kelley, D.A.; Hurd, R.; Kurhanewicz, J.; Nelson, S.J.; Pauly, J.M.; et al. Compressed sensing for resolution enhancement of hyperpolarized 13C flyback 3D-MRSI. J. Magn. Reson. 2008, 192, 258–264.
  100. Hu, S.; Lustig, M.; Balakrishnan, A.; Larson, P.E.Z.; Bok, R.; Kurhanewicz, J.; Nelson, S.J.; Goga, A.; Pauly, J.M.; Vigneron, D.B. 3D compressed sensing for highly accelerated hyperpolarized 13 C MRSI with in vivo applications to transgenic mouse models of cancer. Magn. Reson. Med. 2010, 63, 312–321.
  101. Larson, P.E.Z.; Hu, S.; Lustig, M.; Kerr, A.B.; Nelson, S.J.; Kurhanewicz, J.; Pauly, J.M.; Vigneron, D.B. Fast dynamic 3D MR spectroscopic imaging with compressed sensing and multiband excitation pulses for hyperpolarized 13C studies. Magn. Reson. Med. 2011, 65, 610–619.
  102. Sigfridsson, A.; Weiss, K.; Wissmann, L.; Busch, J.; Krajewski, M.; Batel, M.; Batsios, G.; Ernst, M.; Kozerke, S. Hybrid multiband excitation multiecho acquisition for hyperpolarized 13 C spectroscopic imaging. Magn. Reson. Med. 2014, 73, 1713–1717.
  103. Hu, X.; Levin, D.N.; Lauterbur, P.C.; Spraggins, T. SLIM: Spectral localization by imaging. Magn. Reson. Med. 1988, 8, 314–322.
  104. Von Kienlin, M.; Mejia, R. Spectral localization with optimal pointspread function. J. Magn. Reson. 1991, 94, 268–287.
  105. Farkash, G.; Markovic, S.; Novakovic, M.; Frydman, L. Enhanced hyperpolarized chemical shift imaging based on a priori segmented information. Magn. Reson. Med. 2019, 81, 3080–3093.
  106. Zhang, Y.; Gabr, R.E.; Schär, M.; Weiss, R.G.; Bottomley, P.A. Magnetic resonance Spectroscopy with Linear Algebraic Modeling (SLAM) for higher speed and sensitivity. J. Magn. Reson. 2012, 218, 66–76.
  107. Haldar, J.P.; Liang, Z.-P. Spatiotemporal imaging with partially separable functions: A matrix recovery approach. In Proceedings of the 2010 IEEE International Symposium on Biomedical Imaging: From Nano to Macro, Rotterdam, The Netherlands, 14–17 April 2010; pp. 716–719.
  108. Lee, H.; Song, J.E.; Shin, J.; Joe, E.; Joo, C.G.; Choi, Y.-S.; Song, H.-T.; Kim, D.-H. High resolution hyperpolarized13C MRSI using SPICE at 9.4 T. Magn. Reson. Med. 2018, 80, 703–710.
  109. Song, J.E.; Shin, J.; Lee, H.; Choi, Y.; Song, H.; Kim, D. Dynamic hyperpolarized 13 C MR spectroscopic imaging using SPICE in mouse kidney at 9.4 T. NMR Biomed. 2020, 33, e4230.
  110. Wiesinger, F.; Weidl, E.; Menzel, M.I.; Janich, M.A.; Khegai, O.; Glaser, S.J.; Haase, A.; Schwaiger, M.; Schulte, R.F. IDEAL spiral CSI for dynamic metabolic MR imaging of hyperpolarized [1-13C]pyruvate. Magn. Reson. Med. 2012, 68, 8–16.
  111. Gordon, J.W.; Larson, P.E. Pulse Sequences for Hyperpolarized MRS. Encycl. Magn. Reson. 2016, 5, 1229–1246.
  112. Gordon, J.W.; Vigneron, D.B.; Larson, P.E.Z. Development of a symmetric echo planar imaging framework for clinical translation of rapid dynamic hyperpolarized 13 C imaging. Magn. Reson. Med. 2016, 77, 826–832.
  113. Purvis, L.A.B.; Clarke, W.T.; Biasiolli, L.; Valkovič, L.; Robson, M.D.; Rodgers, C.T. OXSA: An open-source magnetic resonance spectroscopy analysis toolbox in MATLAB. PLoS ONE 2017, 12, e0185356.
  114. Naressi, A.; Couturier, C.; Devos, J.M.; Janssen, M.; Mangeat, C.; De Beer, R.; Graveron-Demilly, D. Java-based graphical user interface for the MRUI quantitation package. Magma Magn. Reson. Mater. Phys. Biol. Med. 2001, 12, 141–152.
  115. Henry, P.-G.; Öz, G.; Provencher, S.; Gruetter, R. Toward dynamic isotopomer analysis in the rat brainin vivo: Automatic quantitation of13C NMR spectra using LCModel. NMR Biomed. 2003, 16, 400–412.
  116. Cavassila, S.; Deval, S.; Huegen, C.; Van Ormondt, D.; Graveron-Demilly, D. Cramér-Rao bounds: An evaluation tool for quantitation. NMR Biomed. 2001, 14, 278–283.
  117. Young, K.; Khetselius, D.; Soher, B.J.; Maudsley, A.A. Confidence images for MR spectroscopic imaging. Magn. Reson. Med. 2000, 44, 537–545.
  118. Nelson, S.J.; Brown, T.R. The accuracy of quantification from 1D NMR spectra using the PIQABLE algorithm. J. Magn. Reson. 1989, 84, 95–109.
  119. Brender, J.R.; Kishimoto, S.; Merkle, H.; Reed, G.; Hurd, R.E.; Chen, A.P.; Ardenkjaer-Larsen, J.H.; Munasinghe, J.; Saito, K.; Seki, T.; et al. Dynamic Imaging of Glucose and Lactate Metabolism by 13C-MRS without Hyperpolarization. Sci. Rep. 2019, 9, 3410.
  120. Harrison, C.; Yang, C.; Jindal, A.; DeBerardinis, R.J.; Hooshyar, M.A.; Merritt, M.E.; Sherry, A.D.; Malloy, C.R. Comparison of kinetic models for analysis of pyruvate-to-lactate exchange by hyperpolarized13C NMR. NMR Biomed. 2012, 25, 1286–1294.
  121. Pagès, G.; Kuchel, P.W. Mathematical Modeling and Data Analysis of Nmr Experiments Using Hyperpolarized 13C Metabolites. Magn. Reson. Insights 2013, 6, MRI.S11084-21.
  122. Larson, P.E.Z.; Chen, H.; Gordon, J.W.; Korn, N.; Maidens, J.; Arcak, M.; Tang, S.; Criekinge, M.; Carvajal, L.; Mammoli, D.; et al. Investigation of analysis methods for hyperpolarized 13C-pyruvate metabolic MRI in prostate cancer patients. NMR Biomed. 2018, 31, e3997.
  123. Hill, D.K.; Orton, M.R.; Mariotti, E.; Boult, J.K.R.; Panek, R.; Jafar, M.; Parkes, H.G.; Jamin, Y.; Miniotis, M.F.; Al-Saffar, N.M.S.; et al. Model Free Approach to Kinetic Analysis of Real-Time Hyperpolarized 13C Magnetic Resonance Spectroscopy Data. PLoS ONE 2013, 8, e71996.
  124. Daniels, C.J.; McLean, M.A.; Schulte, R.F.; Robb, F.J.; Gill, A.B.; McGlashan, N.; Graves, M.J.; Schwaiger, M.; Lomas, D.J.; Brindle, K.M.; et al. A comparison of quantitative methods for clinical imaging with hyperpolarized 13 C-pyruvate. NMR Biomed. 2016, 29, 387–399.
  125. Santarelli, M.F.; Positano, V.; Giovannetti, G.; Frijia, F.; Menichetti, L.; Ardenkjaer-Larsen, J.-H.; De Marchi, D.; Lionetti, V.; Aquaro, G.; Lombardi, M.; et al. How the signal-to-noise ratio influences hyperpolarized 13C dynamic MRS data fitting and parameter estimation. NMR Biomed. 2011, 25, 925–934.
  126. Gallagher, F.A.; Kettunen, M.I.; Brindle, K.M. Imaging pH with hyperpolarized 13 C. NMR Biomed. 2011, 24, 1006–1015.
  127. Gallagher, F.A.; Kettunen, M.I.; Day, S.E.; Hu, D.-E.; Ardenkjaer-Larsen, J.H.; Zandt, R.; Jensen, P.R.; Karlsson, M.; Golman, K.; Lerche, M.H.; et al. Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate. Nat. Cell Biol. 2008, 453, 940–943.
  128. Pourfathi, M.; Kadlecek, S.J.; Chatterjee, S.; Rizi, R.R. Metabolic Imaging and Biological Assessment: Platforms to Evaluate Acute Lung Injury and Inflammation. Front. Physiol. 2020, 11.
  129. Ishii, M.; Emami, K.; Kadlecek, S.; Petersson, J.S.; Golman, K.; Vahdat, V.; Yu, J.; Cadman, R.V.; MacDuffie-Woodburn, J.; Stephen, M.; et al. Hyperpolarized13C MRI of the pulmonary vasculature and parenchyma. Magn. Reson. Med. 2007, 57, 459–463.
  130. Lipso, K.W.; Magnusson, P.; Ardenkjaer-Larsen, J.H. Hyperpolarized 13C MR Angiography. Curr. Pharm. Des. 2015, 22, 90–95.
  131. Markovic, S.; Fages, A.; Roussel, T.; Hadas, R.; Brandis, A.; Neeman, M.; Frydman, L. Placental physiology monitored by hyperpolarized dynamic 13C magnetic resonance. Proc. Natl. Acad. Sci. USA 2018, 115, E2429–E2436.
  132. Madsen, K.E.; Mariager, C.Ø.; Duvald, C.S.; Hansen, E.S.S.; Bertelsen, L.B.; Pedersen, M.; Pedersen, L.H.; Uldbjerg, N.; Laustsen, C. Ex Vivo Human Placenta Perfusion, Metabolic and Functional Imaging for Obstetric Research—A Feasibility Study. Tomography 2019, 5, 333–338.
  133. Park, J.M.; Josan, S.; Mayer, D.; Hurd, R.E.; Chung, Y.; Bendahan, D.; Spielman, D.M.; Jue, T. Hyperpolarized 13C NMR observation of lactate kinetics in skeletal muscle. J. Exp. Biol. 2015, 218, 3308–3318.
  134. Leftin, A.; Degani, H.; Frydman, L. In vivo magnetic resonance of hyperpolarized [13C1]pyruvate: Metabolic dynamics in stimulated muscle. Am. J. Physiol. Metab. 2013, 305, E1165–E1171.
  135. Bastiaansen, J.A.; Cheng, T.; Mishkovsky, M.; Duarte, J.M.; Comment, A.; Gruetter, R. In vivo enzymatic activity of acetylCoA synthetase in skeletal muscle revealed by 13C turnover from hyperpolarized [1-13C]acetate to [1-13C]acetylcarnitine. Biochim. Biophys. Acta Gen. Subj. 2013, 1830, 4171–4178.
  136. Laustsen, C. Hyperpolarized 13C Magnetic Resonance Treatment Response Monitoring: A New Paradigm for Multiorgan Metabolic Assessment of Pharmacological Interventions? Diabetes 2016, 65, 3529–3531.
  137. Lewis, A.J.; Miller, J.J.; McCallum, C.; Rider, O.J.; Neubauer, S.; Heather, L.C.; Tyler, D.J. Assessment of Metformin-Induced Changes in Cardiac and Hepatic Redox State Using Hyperpolarized[1-13C]Pyruvate. Diabetes 2016, 65, 3544–3551.
  138. Bertelsen, L.B.; Nielsen, P.M.; Qi, H.; Nørlinger, T.S.; Zhang, X.; Stødkilde-Jørgensen, H.; Laustsen, C. Diabetes induced renal urea transport alterations assessed with 3D hyperpolarized13C,15N-Urea. Magn. Reson. Med. 2017, 77, 1650–1655.
  139. Larson, P.E.Z.; Gold, G.E. Science to practice: Can inflammatory arthritis be monitored by using MR imaging with injected hyperpolarized 13C-pyruvate? Radiology 2011, 259, 309–310.
  140. Neveu, M.-A.; Beziere, N.; Daniels, R.; Bouzin, C.; Comment, A.; Schwenck, J.; Fuchs, K.; Kneilling, M.; Pichler, B.J.; Schmid, A.M. Lactate Production Precedes Inflammatory Cell Recruitment in Arthritic Ankles: An Imaging Study. Mol. Imaging Biol. 2020, 22, 1324–1332.
  141. Le Page, L.M.; Guglielmetti, C.; Najac, C.F.; Tiret, B.; Chaumeil, M.M. Hyperpolarized 13C magnetic resonance spectroscopy detects toxin-induced neuroinflammation in mice. NMR Biomed. 2019, 32, e4164.
  142. Thind, K.; Chen, A.; Friesen-Waldner, L.; Ouriadov, A.; Scholl, T.J.; Fox, M.; Wong, E.; VanDyk, J.; Hope, A.; Santyr, G. Detection of radiation-induced lung injury using hyperpolarized13C magnetic resonance spectroscopy and imaging. Magn. Reson. Med. 2012, 70, 601–609.
  143. Thind, K.; Jensen, M.D.; Hegarty, E.; Chen, A.P.; Lim, H.; Martínez-Santiesteban, F.; Van Dyk, J.; Wong, E.; Scholl, T.J.; Santyr, G.E. Mapping metabolic changes associated with early Radiation Induced Lung Injury post conformal radiotherapy using hyperpolarized 13C-pyruvate Magnetic Resonance Spectroscopic Imaging. Radiother. Oncol. 2014, 110, 317–322.
  144. Lumata, L.L.; Yang, C.; Ragavan, M.; Carpenter, N.R.; DeBerardinis, R.J.; Merritt, M.E. Hyperpolarized 13C Magnetic Resonance and Its Use in Metabolic Assessment of Cultured Cells and Perfused Organs. In Methods in Enzymology; Academic Press Inc.: Cambridge, MA, USA, 2015; Volume 561, pp. 73–106.
  145. Brindle, K.M. Imaging Metabolism with Hyperpolarized13C-Labeled Cell Substrates. J. Am. Chem. Soc. 2015, 137, 6418–6427.
  146. Katsikis, S.; Marin-Montesinos, I.; Ludwig, C.; Günther, U.L. Detecting acetylated aminoacids in blood serum using hyperpolarized 13C-1H-2D-NMR. J. Magn. Reson. 2019, 305, 175–179.
  147. Shishmarev, D.; Kuchel, P.W.; Pagès, G.; Wright, A.J.; Hesketh, R.L.; Kreis, F.; Brindle, K.M. Glyoxalase activity in human erythrocytes and mouse lymphoma, liver and brain probed with hyperpolarized 13C-methylglyoxal. Commun. Biol. 2018, 1, 232.
  148. Sriram, R.; Sun, J.; Villanueva-Meyer, J.; Mutch, C.; Santos, J.D.L.; Peters, J.; Korenchan, D.E.; Neumann, K.; Van Criekinge, M.; Kurhanewicz, J.; et al. Detection of Bacteria-Specific Metabolism Using Hyperpolarized [2-13C]Pyruvate. ACS Infect. Dis. 2018, 4, 797–805.
  149. Autry, A.; Park, I.; Kline, C.; Chen, H.-Y.; Gordon, J.; Raber, S.; Hoffman, C.; Kim, Y.; Okamoto, K.; Vigneron, D.; et al. Pilot Study of Hyperpolarized 13C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers. Am. J. Neuroradiol. 2021, 42, 178–184.
  150. Ardenkjaer-Larsen, J.H. Hyperpolarized MR—What’s up Doc? J. Magn. Reson. 2019, 306, 124–127.
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